The objectives of the proposed research are to define the genetic structure of natural populations of the human-pathogenic bacteria Legionella pneumophila and allied species, Neisseria gonorrhoeae, Haemophilus influenzae, and Escherichia coli. The method of genetic analysis involves determination of variation in multilocus genotypes, as indexed by the electrophoretic mobility of allelic variants of 20 enzymes in hundreds of individual bacterial isolates. Through application of the theory, laboratory methodology, and statistics of molecular population genetics, the proposed research seeks to develop powerful new genetic markers for studying the epidemiology and systematics of pathogenic bacteria. A major hypothesis being tested is that the genetic population structure of many human-pathogenic bacteria is basically clonal, with very limited chromosomal recombination, the pathogenic species being represented by relatively modest numbers of widely distributed clones carry special virulence factors, the genes of which are often in linkage disequilibrium with the enzyme loci being monitored. Variation in chromosomal genotype is analyzed in relation to serotype, biotype, and other phenotypic characters to assess the effectiveness of these characters in identifying strains in epidemiological and ecological research and to identify possible determinants of pathogenicity. In broad perspective, the proposed research seeks to establish for several pathogenic species of bacteria basic population genetic frameworks within which to organize data on the distribution of cell-surface antignes, toxins, adhesions, plasmids, and other characters that have been implicated as determinants of pathogenicity and disease specificity, while at the same time providing high-resolution marker systems for epidemiological, ecological, and other lines of research.